PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185erbB2/neu Tumor Immunotherapy

Frontiers in Immunology
Yasuhiro NagaiMark I Greene

Abstract

Regulatory T cells (Tregs) are a subpopulation of T cells that are specialized in suppressing immune responses. Here we show that the arginine methyl transferase protein PRMT5 can complex with FOXP3 transcription factors in Tregs. Mice with conditional knock out (cKO) of PRMT5 expression in Tregs develop severe scurfy-like autoimmunity. In these PRMT5 cKO mice, the spleen has reduced numbers of Tregs, but normal numbers of Tregs are found in the peripheral lymph nodes. These peripheral Tregs that lack PRMT5, however, display a limited suppressive function. Mass spectrometric analysis showed that FOXP3 can be di-methylated at positions R27, R51, and R146. A point mutation of Arginine (R) 51 to Lysine (K) led to defective suppressive functions in human CD4 T cells. Pharmacological inhibition of PRMT5 by DS-437 also reduced human Treg functions and inhibited the methylation of FOXP3. In addition, DS-437 significantly enhanced the anti-tumor effects of anti-erbB2/neu monoclonal antibody targeted therapy in Balb/c mice bearing CT26Her2 tumors by inhibiting Treg function and induction of tumor immunity. Controlling PRMT5 activity is a promising strategy for cancer therapy in situations where host immunity against tumors is attenuated...Continue Reading

References

Jan 1, 1975·Immunological Communications·S FujimotoA H Sehon
Jan 11, 2003·Science·Shohei HoriShimon Sakaguchi
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Apr 2, 2004·The Journal of Biological Chemistry·Donghang ChengMark T Bedford
Jun 9, 2004·The Journal of Experimental Medicine·Ann E HermanChristophe Benoist
Mar 25, 2006·Nature Reviews. Immunology·Weiping Zou
Feb 15, 2007·PLoS Biology·Stefan FloessJochen Huehn
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Bin LiMark I Greene
May 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sonia A PerezMichael Papamichail
Oct 3, 2009·Science·Ashutosh ChaudhryAlexander Y Rudensky
Jun 3, 2010·International Journal of Cancer. Journal International Du Cancer·Hiroyoshi Nishikawa, Shimon Sakaguchi
Feb 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alena Cristina Jaime-RamirezWilliam E Carson
Apr 7, 2011·Nature Communications·Takashi SekiyaAkihiko Yoshimura
Oct 30, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·C TanchotE Tartour
Dec 14, 2012·Nature Reviews. Cancer·Yanzhong Yang, Mark T Bedford
Aug 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Han WeiTao Lu
Mar 29, 2014·The Journal of Clinical Investigation·Alena GrosSteven A Rosenberg
Oct 24, 2014·EMBO Molecular Medicine·Daniel BilbaoNadia Rosenthal
Feb 11, 2015·Cellular and Molecular Life Sciences : CMLS·Nicole StopaDavid Shechter
Apr 22, 2015·ACS Medicinal Chemistry Letters·David SmilMatthieu Schapira
Apr 29, 2015·Nature Chemical Biology·Elayne Chan-PenebreKenneth W Duncan
Dec 22, 2015·Nature Reviews. Immunology·Michael D RosenblumAbul K Abbas

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Citations

Jul 28, 2019·Nature Reviews. Molecular Cell Biology·Ernesto Guccione, Stéphane Richard
Aug 7, 2019·Clinical and Experimental Immunology·G DengM I Greene
Apr 25, 2020·Frontiers in Immunology·Yukinori TanakaTaku Kambayashi
Jul 10, 2020·Science Translational Medicine·Hyungsoo KimZe'ev A Ronai
Nov 5, 2019·Frontiers in Immunology·Guoping DengMark I Greene
Aug 9, 2020·Clinical Science·Chunyun Zhang, Shougang Zhuang
Jan 21, 2021·Cellular Oncology (Dordrecht)·Yuanyang Yuan, Hong Nie
Dec 31, 2020·Life Science Alliance·Baskar ChakrapaniArunkumar Dhayalan
Jan 17, 2021·International Journal of Molecular Sciences·Marco GargaroFrancesca Fallarino
Jan 20, 2021·The Journal of Allergy and Clinical Immunology·Shota ToyoshimaYoshimichi Okayama
Feb 3, 2021·The FEBS Journal·Biaolong DengBin Li
Feb 23, 2020·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Qianru HuangBin Li
Mar 21, 2021·Nature Reviews. Drug Discovery·Qin WuDalia Barsyte-Lovejoy
Sep 6, 2020·Trends in Immunology·Shouvonik SenguptaMireia Guerau-de-Arellano
May 20, 2021·Experimental & Molecular Medicine·Jee Won HwangYong Kee Kim
Jun 29, 2021·Frontiers in Immunology·Yujing ZhangRong Jia
Jul 30, 2021·European Journal of Immunology·Weiqi ZhangBin Li
Sep 22, 2021·Antioxidants & Redox Signaling·Xiaoqing Zheng, Amr H Sawalha

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Methods Mentioned

BETA
ubiquitination
transfection
flow
fluorescence-activated cell sorter
PMA
FACS
flow cytometry
PCR
Assay
immunoprecipitation

Software Mentioned

EBSeq
Excel

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